Canine transmissible venereal tumor (CTVT) is transmitted via mating, wound-to-wound or saliva contact. The growth model of CTVT includes progressive phase (P phase), steady phase (S phase), and regressive phase (R phase). Major histocompatibility complex (MHC) molecule expresses on the surface of CTVT cells. Tumor cells lack MHC antigen during P phase, while both MHC classes I and II are increased dramatically during R phase (the 12th week after inoculation), and they are continued to increase till regression of CTVT. The MHC molecules expressed are important for helper CD4 T cells and cytotoxic T lymphocytes in tumor recognition. The low amount of MHC of tumor during P phase evades the attack of the host immune system. On the other hand, TGF-β highly secreted by tumors during P phase can inhibit both NK cells and dendritic cells (DCs), which causes tumor related antigens were not presented to T cells, followed by immune tolerance. The mechanism is summarized in FIG. 1, where TGF-β highly secreted by CTVT tumors inhibits the IFN-γ-induced MHC expression, and therefore inhibit the killing activity since no MHC is expressed. However, tumor infiltrating lymphocytes (TIL) in host secreted large amount of IL-6 to counteract these effects in an unknown mechanism. The functions of IFN-γ and mononuclear cells are recovered, and CTVT cells are killed by T cells and NK cells, followed by entering the R phase.
In addition, dendritic cells can be inhibited by TGF-β secreted by CTVT. DCs are the most important antigen presenting cells (APCs). Part of the tumor cells will be dead during the early stage of tumor growth due to the genetic instability and unbalanced nutrients and release tumor associated antigen. The tumor associated antigen will be ingested by immature dendritic cells (iDCs) through endocytosis. These iDCs migrate to lymph nodes to become mature dendritic cells (mDCs) with the help of chemochytokine receptor 7 (CCR7). High levels of co-stimulatory molecules such as CD80/CD83/CD86 will be expressed in mDCs and effectively activate native CD4+ T cells, followed by activate CD8+ T cells to become cytotoxic T cells to kill tumor cells specifically. On the other hand, CD8 T cell can be activated by DCs directly through cross-priming to kill tumor cells. However, high concentration of TGF-β secreted by tumor inhibits monocyte-derived dendritic cells, including lowering the surface molecules of DCs such as CD80/CD86/MHC II, or lowering the ability of antigen endocytosis and antigen presentation. Then the specific killing ability will be lost since DCs are unable to present antigens to T cells effectively. Therefore, activating DCs cells effectively to present antigens for T cells and killing tumor cells after recognition are key issues for the study. In addition, how to present the unknown antigens to T cells is also an important issue since most of the tumor antigens are unknown.